Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.583 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
NOAEC
Value:
43.75 mg/m³
Explanation for the modification of the dose descriptor starting point:

The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 2 in case of oral to inhalation extrapolation. Standard respiratory volume of a rat, corrected for 8 h exposure, as proposed in the REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) is considered to be 0.4 m³/kg bw. Correction for activity driven differences of respiratory volumes in workers compared to workers in rest was considered to be 6.7 m³/10 m³. Therefore, the modified dose descriptor starting point is 43.75 mg/m³ (= 50 / 2 / 0.4 x (7/10)).

AF for differences in duration of exposure:
6
Justification:
Difference in duration from subacute to chronic
AF for other interspecies differences:
2.5
Justification:
Remaining difference
AF for intraspecies differences:
5
Justification:
Worker population
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.16 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEL
Value:
1 250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Based on the exposure model from AG Textilien des Bundesinstituts für Risikobewertung (BfR), the dermal penetration rate for dyes through the skin was found to be less than 2 %. Therefore, a factor of 25 was taken into consideration as worst case for the oral to dermal route to route extrapolation. Therefore, the modified dose descriptor starting point is 1250 (25 x 50) mg/kg bw/day.

AF for differences in duration of exposure:
6
Justification:
Difference in duration from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rats to humans
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
5
Justification:
Worker population
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

According to the REACH Guidance on information requirements and chemical safety assessment, a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible. 

Short-term toxicity:

According to the REACH guideline (R8, Appendix R 8-8), a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential risk for high peak exposures. Since the substance is not classified for acute dermal, inhalation, and oral toxicity, no short-term DNELs needs to be derived for these routes of exposure.

The substance is also not classified as irritating to the skin but is classified as skin sensitizer, however, since only a guinea pig maximization test result is available, no DNEL could be derived.

Long-term toxicity:

A repeated dose toxicity study by oral route is available in rats and a NOAEL of 50 mg/kg bw was determined. Since only a sub-acute oral toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for dermal and inhalation route. According to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, it is proposed in the absence of route-specific information on the starting route, to include a default factor of 2 in the case of oral-to-inhalation extrapolation. Based on the exposure model from AG Textilien des Bundesinstituts für Risikobewertung (BfR), the dermal penetration rate for dyes through the skin was found to be less than 2 %. Therefore, a factor of 25 was taken into consideration as worst case for the oral to dermal route to route extrapolation. This approach will be taken forward to DNEL derivation.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.144 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
NOAEC
Value:
21.739 mg/m³
Explanation for the modification of the dose descriptor starting point:

The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 2 in case of oral to inhalation extrapolation. Standard respiratory volume of a rat, corrected for 24 h exposure, as proposed in the REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) is considered to be 1.15 m³/kg bw. Therefore, the modified dose descriptor starting point is 21.739 m³/kg bw (= 50 / 2 / 1.15).

AF for differences in duration of exposure:
6
Justification:
The extrapolation to chronic exposure is based on a sub-acute toxicity study.
AF for intraspecies differences:
10
Justification:
Default assessment factor for consumers is used.
AF for remaining uncertainties:
2.5
Justification:
Default assessment factor is used.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

As the long-term DNEL  is normally sufficient to ensure that effects do not occur and no acute effects were noted in the repeated dose study or acute studies, no acute hazard during short term exposure is expected if long term DNELs are maintained.

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.083 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
1 250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Based on the exposure model from AG Textilien des Bundesinstituts für Risikobewertung (BfR), the dermal penetration rate for dyes through the skin was found to be less than 2 %. Therefore, a factor of 25 was taken into consideration as worst case for the oral to dermal route to route extrapolation.

AF for differences in duration of exposure:
6
Justification:
The extrapolation to chronic exposure is based on a sub-acute toxicity study.
AF for interspecies differences (allometric scaling):
4
Justification:
An assessment factor for allometric scaling is used.
AF for intraspecies differences:
10
Justification:
Default assessment for consumers is used.
AF for remaining uncertainties:
2.5
Justification:
Default assessment factor is used.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation is required.

AF for differences in duration of exposure:
6
Justification:
The extrapolation to chronic exposure is based on a sub-acute toxicity study.
AF for interspecies differences (allometric scaling):
4
Justification:
An assessment factor for allometric scaling is used.
AF for other interspecies differences:
10
Justification:
The default assessment factor for consumers is used.
AF for remaining uncertainties:
2.5
Justification:
The default assessment factor is used.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

According to the REACH Guidance on information requirements and chemical safety assessment, a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible. 

Short-term toxicity:

According to the REACH guideline (R8, Appendix R 8-8), a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential risk for high peak exposures. Since the substance is not classified for acute dermal, inhalation, and oral toxicity, no short-term DNELs needs to be derived for these routes of exposure.

The substance is also not classified as irritating to the skin but is classified as skin sensitizer, however, since only a guinea pig maximization test results are available, no DNEL could be derived.

Long-term toxicity:

A repeated dose toxicity study by oral route is available in rats and a NOAEL of 50 mg/kg bw was determined.

Since only a sub-acute oral toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for dermal and inhalation route.According to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, it is proposed in the absence of route-specific information on the starting route, to include a default factor of 2 in the case of oral-to-inhalation extrapolation. Based on the exposure model from AG Textilien des Bundesinstituts für Risikobewertung (BfR), the dermal penetration rate for dyes through the skin was found to be less than 2 %. Therefore, a factor of 25 was taken into consideration as worst case for the oral to dermal route to route extrapolation. This approach will be taken forward to DNEL derivation.